While substantial evidence exists confirming the regulation of macronutrient intake, the mechanism by which this occurs is poorly understood. In many cases, interpretation of these data has been clouded by confounding variables due to improper design of test diets. In addition, much work has centered around regulation of protein and carbohydrate intake, but the role of fat has been largely unexplored. We provide some of the first data to suggest that type and amount of dietary fat, fed for a very short time, strongly influence protein and carbohydrate intake. Further, diets are formulated to minimize confounding variables; holding calories and micronutrient levels constant. Studies are described to determine the role of sensory cues and metabolic input by which this response occurs and to examine the time course of the response and the importance of taste receptors. Control from hepatic mechanisms will be tested by examining hepatic metabolism and neural output in fat fed animals. The overall goal of the proposal is to further clarify the mechanism(s) controlling selection of all the macronutrients. These data may be significant to the study of obesity, particularly diet-induced obesity, the most common type in the human population. It is well documented that highly palatable foods of high carbohydrate and fat content can induce obesity in freely feeding rats and that human obesity is often characterized by carbohydrate craving. Understanding the mechanism(s) involved in regulation of macronutrient selection and the role(s) of the macronutrients, may aid in the treatment of this disease.